Category Archives: Antimicrobial Resistance

“Carbapenem Conundrums”

Antimicrobial Resistance, Antimicrobial Stewardship, The Science of Microbiology,

Last week, while on-call I recommended a carbapenem for three different patients within the space of 30 minutes. Yes, it happens sometimes! Most empiric antibiotic choices do not require the inclusion of a carbapenem, but key factors to consider are ESBL history, travel or hospitalisation in areas with high ESBL endemicity, and how sick the patient is.

It is interesting to look at the psychology of carbapenem prescribing. Some doctors prescribe carbapenems because they are afraid of giving treatment to their patients that might not cover all resistance profiles. Others are afraid of prescribing carbapenems because they are traditionally the top line treatment and scared of criticism from antimicrobial stewards like myself!

But if you have to use a carbapenem, which one should you use?

The main choice in New Zealand is generally between meropenem and ertapenem. Imipenem-cilastatin is rarely used now in New Zealand, mainly due to its seizure risk. (There is a little evidence that it is the optimal carbapenem for disseminated nocardiosis and a few other isoteric indications) Other carbapenems outside these three have limited availability in NZ hospitals, or at least the ones I work in. This may be different elsewhere in the world.

Choosing between meropenem and ertapenem:

Here are most of the key factors I take into account when choosing between the two

Organism coverage-If I need to empirically cover Pseudomonas or Enterococci or Acinetobacter spp., then meropenem is a better option than ertapenem due to its broader coverage.

CNS penetration-Meropenem is a better option than ertapenem due to better CNS penetration. I had a patient with E.coli meningitis recently who required meropenem until the susceptibilities were known.

Hypo-albuminaemia– Ertapenem is highly protein bound compared to meropenem, so in hypo-albuminaemic states, the free fraction of ertapenem is increased, and it is chucked out through the kidneys leading to a decreased half-life. Therefore, meropenem is preferred in hypo-albuminemia. I use 25 g/l as an arbitrary cut-off.

Dosing frequency– If reduced dosing frequency is preferred due to patient compliance/outpatient therapy etc, then once daily ertapenem is preferable to three times a day meropenem.

Penetration into biliary tissue-Ertapenem has poor penetration into biliary tissue compared to meropenem, so I prefer meropenem for biliary infections.

Duration of treatment- Meropenem is more stable than ertapenem against resistance mechanisms such as upregulation of efflux pumps or porin channel loss. These mechanisms can become an issue with prolonged treatment and should be taken into account when choosing between the two.

Although the above points might suggest otherwise, I actually recommend more ertapenem than meropenem. Ertapenem is absolutely fine for most straightforward cases of urosepsis where empiric ESBL coverage is required.

One other point. If you do need to utilise a carbapenem, then regular review and timely de-escalation based on the patient’s condition and/or susceptibility results is important to optimise antimicrobial stewardship.

Michael

“Reporting susceptibilities on UTIs, not urinary isolates…”

Antimicrobial Resistance, Antimicrobial Stewardship, , , ,

Urines arrive at diagnostic microbiology laboratories in considerable numbers. My own lab in New Zealand processes a couple of thousand urines a week. A significant proportion of these will have positive cultures. Therefore, the potential for the laboratory to promote good antimicrobial stewardship with respect to urinary tract infection is considerable.

My mantra on this is as follows: “The microbiology lab should never release antibiotic susceptibilities on a positive culture from a urine sample unless there is reasonable evidence accompanying the request that the patient has a UTI.”

The fact that the urine sample has turned up at the microbiology lab is insufficient evidence per se that the patient has a UTI. Urines get sent to microbiology laboratories for all sorts of spurious reasons, see below for a few examples:

  • Urines often get sent “automatically” from acute receiving wards as part of a blanket laboratory screen, where the patient may have a diverse spectrum of symptoms such as chest pain, shortness of breath, collapse, etc.
  • Urines can get sent from Long Term Care Facilities when someone decides to dipstick all their patients and send the urine samples with positive dipsticks to the lab for culture. Yes, it happens, and a lot more often than you might think!
  • Urine from indwelling catheters can get sent when the patient has a blocked catheter, or the catheter bag is cloudy.
  • Urines from patients attending outpatient clinics should also raise a flag. With the exception of urology clinics, patients who attend a pre-planned elective clinic appointment generally do not have an acute UTI. The same principle can apply for patients who are in hospital wards for other reasons.
  • Urines where the clinicians are looking for other tests, i.e. albumin/creatinine ratio, and due to laboratory processes the urine ends up getting cultured as well…

So, my argument is that if a urine sample turns up at the laboratory without any clinical details or with inappropriate clinical details, the lab is under no obligation whatsoever to release antibiotic susceptibilities on any organisms grown. 

The best approach of course is not to process the sample at all unless relevant clinical details are received. I would regard all of the following clinical details as being unacceptable to justify proceeding to urine culture:

  • No clinical details
  • Cloudy urine
  • Concentrated urine
  • Dark urine
  • Smelly urine
  • Urine dipstick urinalysis results only
  • Routine/monitoring/screening urine
  • Fatigue
  • Increased CRP
  • Lots of other non-specific symptoms!

The easy option for the lab of course is just to accept the sample, report the organisms, and the accompanying susceptibilities. However, this is almost certainly not the best way…

Michael

“Do we perform too much antimicrobial susceptibility testing?”

Antimicrobial Resistance, Confessions of a Microbiologist, The Science of Microbiology, , ,

As lab workers, we like to be helpful. In general, we want to provide as good a service as possible. But sometimes I think we try a little too hard…

One of our key areas of work is antimicrobial susceptibility testing. This is our bread and butter of course. This is one thing that we can do but no one else can, and we like to show off our skills! But there are many circumstances where performing antimicrobial susceptibility testing adds little value for the patient and thus unnecessarily uses up valuable laboratory resources.

Polymicrobial cultures The clinical value of antimicrobial susceptibility testing is inversely proportional to the number of different organism types present in the sample. This includes sterile site samples. Many times in my career I have been asked to do susceptibilities on samples which have grown several different organisms. I almost always push back on this. It should very much be the exception as opposed to the norm.

Eye and Ear Swabs Conjunctivitis and otitis externa are primarily managed by topical preparations, which can even be antiseptics as opposed to antibiotics. In-vitro susceptibility testing correlates poorly with response to topical antibiotics. Antimicrobial susceptibility testing on ear and eye swabs should only happen in a small minority of cases.

Enterobacteriaceae, enterococci & pseudomonas in superficial wound swabs These organisms cause infection in only a very small proportion of samples that they are actually found in. Susceptibilities should only be performed when there is compelling evidence from the clinical details that they are causing problems. 

Enterococci in urines In contrast to wounds, enterococci commonly cause urinary tract infections (they can also represent contamination). However, because amoxycillin achieves concentrations in urine which exceed the MICs of most Enterococcus faecalis and Enterococcus faecium isolates (check out this reference), susceptibility testing is essentially futile, unless the clinical details suggest the patient has a penicillin allergy. A simple comment to this effect will suffice.

Beta-haemolytic streptococci Because beta-haemolytic streptococci are inherently susceptible to beta-lactams, susceptibility testing for these antibiotics is somewhat academic in the majority of simple wound/soft tissue infections.  I would do if the clinical details suggested penicillin allergy.

Anaerobes Anaerobes rarely require formal susceptibility testing. Bacteroides fragilis has predictable response to beta-lactam/beta-lactamase inhibitor combinations. and is often part of a polymicrobial infection anyway (see polymicrobial cultures). In our lab anaerobic susceptibility testing is most often performed for C. acnes causing joint infections, where we test penicillin (almost always susceptible, maybe we don’t need to test…) and clindamycin (very occasionally resistant).

Coagulase negative staphylococci from blood cultures Again these should only be performed when it is clear that the coagulase negative staph is the suspected pathogen (prosthetic material, premature neonates, etc.) which will only be the small majority of the total number of isolates.

Pseudomonas in sputa Once a patient with COPD becomes colonised with Pseudomonas aeruginosa in their sputum, it is generally there to stay. Pseudomonas susceptibility testing should only be done when it is clear from the clinical details that it is causing a problem, i.e. the patient is failing standard management. We also need to review susceptibility testing protocols on pseudomonas isolates from patients with bronchiectasis and cystic fibrosis. There is now increasing evidence that annual susceptibility testing on Pseudomonas isolates from Cystic Fibrosis patients is more than sufficient.

Candida from vaginal swabs It’s not just bacteria! Recurrent vaginal candidiasis is a common problem, and we are often asked to perform antifungal susceptibilities on such isolates. In my opinion it is hardly ever justified. Nystatin based topical therapy often works in these patients. Candida albicans isolates are usually susceptible to generous dosing of azoles. It is only Nakaseomyces glabrata (formerly known as Candida glabrata), where I occasionally acquiesce and perform susceptibility testing…

Of course, we can perform antimicrobial susceptibility testing but not report the results, having them stored just in case. But my view is that we should minimise this approach as it is generally wasteful. We should perform antimicrobial susceptibility testing when we are confident that we are going to report the results of at least some of the antibiotics from a testing panel.

At my lab we have progressed a lot in this area over the past decade and now perform minimal amounts of antimicrobial susceptibility testing in all of the areas above. What about your own lab? Is there room for improvement, and can you think of other areas where too much antimicrobial susceptibility testing is performed, that I have not thought of?

Michael